Viral infections of the respiratory tract are responsible for significant mortality and morbidity worldwide [1]. Despite extensive studies in the past decades that have identified a number of etiologic agents, including rhinoviruses, coronaviruses, influenza viruses, parainfluenzaviruses, respiratory syncytial virus and adenoviruses, approximately 30% of all cases cannot be accounted for by these agents suggesting that additional respiratory pathogens are likely to exist [2]. In fact, since 2001, six previously undescribed viruses have been identified by analysis of clinical specimens from the human respiratory tract: human metapneumovirus [3], SARS coronavirus [4], coronavirus NL63 [5], coronavirus HKU1 [6] and human bocavirus [7], and KI virus [35]. In some instances, new molecular methods such as VIDISCA [5], pan-viral DNA microarrays [8], and high throughput sequencing [7, 35], have played key roles in the identification of these agents. The advent of these new technologies has greatly stimulated efforts to identify novel viruses in the respiratory tract and in other human disease states.
Viruses in the family Polyomaviridae possess double stranded DNA genomes and infect a variety of avian, rodent and primate species. To date, two polyomaviruses, BK virus and JC virus, have been unambiguously described as human pathogens. BK and JC viruses are ubiquitous worldwide, and in adult populations seroprevalence rates approaching 75% and 100%, respectively have been reported [9]. Although human polyomaviruses have been suggested to utilize a respiratory route of transmission, detection of BK and JC polyomavirus nucleic acids in the respiratory tract has rarely been reported [10,11]. Infection with these two viruses is predominantly asymptomatic, although in the context of immunosuppression a number of syndromes have been clearly linked to these viruses. JC virus causes primary multifocal leukoencephalopathy while BK virus has been associated with a variety of renal disorders, most importantly tubular nephritis, which can lead to renal transplant failure and hemorrhagic cystitis in hematopoietic stem cell transplant recipients [12]. These viruses are believed to persist in a latent phase primarily in the kidney and can periodically undergo reactivation. Excretion of BK and JC viruses in urine has been reported in up to 20% of the general population [13] [14]. Besides JC and BK virus, in the late 1950s, ˜100 million people in the United States and many more worldwide may have been exposed to SV40, a polyomavirus that naturally infects rhesus monkeys, via contaminated polio vaccines, leading to widespread debate about whether or not SV40 is capable of sustained infection and replication cycles in humans [15].
Much of the interest in polyomaviruses and SV40 in particular derive from the transforming properties carried by the early transcriptional region of the viral genome that encodes for the small and large T antigens. T antigen is capable of binding both p53 and Rb proteins and interfering with their tumor suppressor functions. The early region alone is sufficient to transform established primary rodent cell lines [16] and in concert with telomerase and ras transforms primary human cells [17]. This has lead to controversy over whether any human tumors are associated with SV40 infection [18].
Identification of viruses associated with respiratory infections facilitates more accurate diagnosis and treatment and paves the way for new therapeutic options.